Oral leukotriene inhibitor (MK-886) blocks allergen-induced airway responses.
|
| Abstract |
To elucidate the role of leukotrienes (LT) in allergic asthma in humans the effect of MK-886, an LT biosynthesis inhibitor, was evaluated on antigen-induced early (EAR) and late (LAR) asthmatic reactions and bronchial responsiveness to histamine. Eight atopic men participated in a two-part, double-blind, placebo-controlled, crossover trial. MK-886 was administered in two oral doses of 500 mg and 250 mg, 1 h before and 2 h after allergen inhalation, respectively. Biochemical effects of MK-886 were evaluated by the inhibition of urinary LTE4 excretion and calcium ionophore-stimulated LTB4 biosynthesis in whole blood ex vivo. MK-886 significantly inhibited the EAR by 58.4% (AUC0-3 h) and the LAR by 43.6% (AUC3-7 h) when compared with placebo (p < 0.01). There was no difference in PC20 histamine 30 h post allergen challenge between MK-886 and placebo (0.33 and 0.27 doubling doses, p > 0.1). MK-886 inhibited calcium ionophore-stimulated LTB4 production in whole blood (54.2 +/- 25.6%) for up to 6 h post allergen challenge. LTE4 excretion in urine was inhibited by 51.5% during the EAR by as much as 80% during the LAR. This indicates that LT play a role in allergen-induced asthmatic reactions in humans in vivo and that LT synthesis inhibitors such as MK-886 should be further explored for the treatment of asthma.
|
|---|---|
| Authors | B S Friedman, E H Bel, A Buntinx, W Tanaka, Y H Han, S Shingo, R Spector, P Sterk |
| Journal | The American review of respiratory disease (Am Rev Respir Dis) Vol. 147 Issue 4 Pg. 839-44 (Apr 1993) ISSN: 0003-0805 [Print] United States |
| PMID | 8385430 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!